Congenital Nevi Research Articles

Alpelisib decreases nevocytes of congenital melanocytic nevi.

Multiple, large or giant congenital melanocytic nevi (CMN) are uncommon and affected patients can show progressive growth and thickening, associate neurocutaneous melanocytosis or develop melanoma. Current treatment modalities are mostly complex surgeries that frequently do not solve the disease and its risks completely. Thus, investigation on new treatment options for CMN and its complications must continue. MAPK pathway inhibitors are being investigated, also targeting PI3K-AKT. Omipalisib (PI3K inhibitor, with no indications approved yet) has been studied for CMN invitro and in mice with promising results. However, alpelisib, a PI3K inhibitor approved with an adequate safety profile for patients with severe manifestations of PROS (PIK3CA-Related Overgrowth Spectrum), had not yet been tested for CMN. To evaluate the effect of alpelisib in nevocytes of congenital melanocytic nevi. Nevomelanocytic tissue samples of 10 patients were collected prospectively and, following a previously reported preclinical exvivo model, explants were placed in organotypic culture for 5 days, with or without alpelisib. Consecutively, tissue sections were stained and using scanned images with Qupath and ImageJ softwares, representative regions from the dermis were analysed (using Wilcoxon test and Spearman's correlation). When comparing alpelisib-treated explants with respect to control explants, we found a decrease in cell density (p = 0.0273), in density of SOX10+-cells (p = 0.0391) and also in the % of S-100+ area (p = 0.0078), in alpelisib samples. The three markers showed a positive correlation (p < 0.05). This study provides first-time evidence that alpelisib induces nevocyte reduction in CMN from patient-derived explants, probably inducted by autophagy. Alpelisib is an approved drug with an adequate safety profile used in another mosaicism affecting PI3K (PROS). Further studies are needed to evaluate its efficacy in treating CMN and potentially, their complications, either with local or systemic administration, alone or in combination.

10141-GMC-13 MULTIREGIONAL GENOMIC ANALYSIS: A NOVEL APPROACH FOR DETECTING PATHOGENIC DRIVER MUTATION ASSOCIATED WITH MALIGNANT PROGRESSION IN NEUROCUTANEOUS MELANOSIS

Abstract Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via ventriculo-peritoneal shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three pathogenic mutations, GNAQ R183Q, S1PR3 G89S and NRAS G12V were found. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discover novel driver mutations associated with tumorigenesis and targeted therapy.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study

BackgroundPediatric melanoma presents with distinct clinical features compared to adult disease. ObjectiveCharacterize risk factors and negative outcomes in pediatric melanoma. MethodsMulticenter retrospective study of patients under 20 years diagnosed with melanoma between 1/1/1995 – 6/30/2015 from 11 academic medical centers. ResultsMelanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common, and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (p=0.046) compared to controls. LimitationsRetrospective nature, cohort size, control selection, and potential referral bias. ConclusionPediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Vitamin D status in children with congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are rare, pigmented birthmarks that can predispose patients to melanoma of the central nervous system and skin. Data from non-CMN melanoma cohorts suggest that vitamin D levels may be connected to outcome, prompting this study of 25-hydroxyvitamin D levels in plasma samples from 40 children with CMN. While 27% were insufficient and 13% deficient, this was representative of European populations, and UK supplementation guidelines are already in place. Our data support routine vitamin D supplementation for all CMN patients during winter months, without routine serum measurement.

MAPK-Activating Gene Fusions in Congenital Nevi

MAPK-Activating Gene Fusions in Congenital Nevi

Óriás congenitális nevusból, csecsemőkorban kialakult melanoma malignum, esetbemutatás és az irodalom áttekintése

Authors present a case of a 37- year-old young female patient, who presented to the emergency department with transient dizziness. The performed cranial MRI confirmed the presence of a solitary brain metastasis. PET CT revealed an FDG-avid active lesion in the lung, with slightly enlarged lymph nodes. The brain tumor was surgically removed and histologically it corresponded to malignant melanoma metastasis. According to tumor board decision combined immunotherapy was initiated. Dermatological examination revealed that the patient was being treated for a histologically neuro-mixoid-appearing melanoma that developed at 3 months of age from a giant congenital nevus at birth and later metastasized regionally. Multiple radical surgeries were performed and she received vincristine and platina based chemotherapy. She was symptom-, and complaint-free for decades under regular check-ups until the onset of vertigo. In connection with the case the authors discuss the specific features of childhood melanomas, in particular the early-onset forms arising from congenital giant.

A clinical and biologic review of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway caused by postzygotic somatic mutations. The estimated incidence of newborns with CMN is 1%-2%. The main complications of CMN include proliferative nodules, melanomas, and neurocutaneous melanosis, and the latter two are the most troublesome issues to address. Treatments are primarily taken into account for aesthetic purposes and the reduction of melanoma risk. Due to the much lower incidence of malignant transformation observed in recent studies than in previous data, clinical management paradigms for CMN patients have gradually shifted towards conservative observation and close monitoring. Surgery and lasers are still the main treatments, and targeted therapy may be a promising strategy to help manage complications. With the increase in awareness of mental health, increasing focus has been placed on the quality of life (QoL) and psychological issues of both CMN patients and their parents. Recent studies have revealed that families coping with CMN might endure intense pressure, a major loss in QoL, and psychological problems after diagnosis and during treatment. Here, we sought to present an overview of genetic basis, complications, treatments, and psychological issues related to CMN and hope to provide better management for patients with CMN.

Resurfacing of Sleeve-Like Circumferential Giant Congenital Melanocytic Nevi on the Upper Extremity With Pre-Expanded Pedicled Flap.

As the relative shortage of healthy tissue obviates the option of local soft tissue coverage, reconstruction of circumferential giant congenital melanocytic nevi (GCMN) on the upper extremity remains particularly challenging. Here the authors report a 3-stage procedure involving pre-expanded pedicled flap from the torso for the reconstruction of upper extremity after circumferential GCMN excision in pediatric patients. The giant nevus was completely removed and the size of the excised nevus was 31 × 14.5cm. The donor site was primarily closed. No major complication was encountered. Reconstruction with expanded pedicled flap achieved satisfactory results, both functionally and cosmetically.

Histopathological characteristics analysis of giant melanocytic naevi in children.

The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis. This study aimed to investigate the pathological features of GCMN, including its satellite lesions. Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed. In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus. We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.

Reconstruction of a medium-sized congenital melanocytic nevus defect using a thin thoracodorsal artery perforator free flap: a case report

Congenital melanocytic nevus (CMN) is a benign condition that either is present at birth or develops in the first weeks of life. Surgical removal is typically performed to improve cosmetic appearance and reduce the risk of malignant transformation. In this report, we present the case of a 26-year-old woman with a medium-sized CMN on her left breast. The nevus measured 14×8 cm, and the patient desired a single-stage excision. However, this approach would result in a large skin defect that would be challenging to reconstruct using a local flap or skin graft. Moreover, it could potentially compromise the maintenance of natural sagging and the contour of the breast. Consequently, we opted to place a thin thoracodorsal artery perforator free flap following the removal of the CMN. The patient was satisfied with the overall surgical results. By utilizing this free flap for reconstruction, we successfully preserved the natural shape and contour of the breast without complications such as postoperative hypertrophic scarring or contracture at the recipient site.

Scleritis in children: Etiology, pathogenesis, clinical features, diagnostic, and treatment algorithm

AIM: To analyze the etiology and pathogenesis and identify clinical and diagnostic features, development of a diagnostic algorithm, and personalized treatment of scleritis in children.&#x0D; MATERIALS AND METHODS: Twelve children with mono- and bilateral scleritis with disease duration of 39 months were observed. Biomicroscopy, ophthalmoscopy, and ultrasonography of the eyes were performed. The examination plan included consultations with a rheumatologist, otorhinolaryngologist, and dentist and laboratory blood analysis in the enzyme immunoassay to detect the presence of IgG and IgM antibodies to herpes viruses and markers of their reactivation.&#x0D; RESULTS: Chronic scleritis in 58.4% of the patients was associated with immunoinflammatory rheumatic diseases: 41.7% with juvenile idiopathic arthritis and 16.7% with psoriatic arthritis. In some cases scleritis was associated with chickenpox, surgical treatment of congenital pigmented nevus of the skin of eyelids,n on the conjunctiva and oculomotor muscles, otogenic neuritis of the facial nerve. Сlinical features of anterior deep scleritis and symptoms of bacterial scleritis are described. Personalized schemes for the diagnosis and treatment of scleritis in children have been developed. Conservative treatment included instillation of glucocorticoids and non-steroidal anti-inflammatory drugs. In addition, to anti-inflammatory therapy, antibacterial drugs are prescribed only in the presence of clinical signs of bacterial scleritis; in other cases, their use is inappropriate. The indications for antiviral therapy included laboratory confirmation of herpes infection reactivation. Personalized etiotropic therapy made it possible to achieve remission of scleritis in 914 days.&#x0D; CONCLUSION: This study analyzed the etiopathogenesis of scleritis, described the characteristic clinical features of anterior deep scleritis in children, and developed personalized diagnostic and treatment schemes.

Challenges in adult services for a young adult with a rare skin disease.

Maddie, a 17-year-old patient with congenital melanocytic naevi who is a Young Ambassador with Caring Matters Now, wrote this article while on work experience with the Support Pathway Practitioner for the charity. This article discusses how young adult members should be supported while transitioning to adult services and the challenges faced by young people affected by a rare skin disease as they transition from specialized care to local services.

A gyermekkori nagyméretű és óriás festéksejtes anyajegyek eltávolításának szempontjai

The removal of common nevi is necessary only in case of irritation, changes causing complaints, or dermatological recommendations, in addition to regular inspections. In case of the need for surgical removal of special birthmarks (e.g. Spitz nevus, Halo nevus, etc.), a dermatological examination and recommendation are also essential. Congenital melanocytic nevus is a special entity. In 1-3% of newborn cases we encounter the small (&lt;1.5 cm) congenital melanocytic nevus, and less often a giant (≥40 cm) nevus. The number, localization and morphology of congenital melanocytic nevi are more important than size in terms of the probability of melanoma occurrence. The treatment of these nevi varies individually and requires teamwork (e.g. dermatologist, oncologist, surgeon, anesthesiologist, pediatrician). All skin incisions leave a scar, and the characteristics of lifelong scars are influenced by many factors. These include age and surgical technique. For plastic surgery performed in childhood, it is advisable to choose the simplest technique – but the one that leads to the most favorable later results – when possible, to avoid complicated flap plasties and skin replacement procedures. When developing the surgical strategy, it is essential to involve the parent and the child in addition to the allied professions, as well as keeping in mind the characteristics of childhood. In the optimal case, the completion of the reconstruction should carry out before get into community, but at the latest by the teenage years.

Application of indocyanine green angiography in repair of facial soft tissue defect using superficial temporal artery based forehead flap

To explore the feasibility of using indocyanine green angiography in mapping the superficial temporal vessels and assisting design and harvesting of the superficial temporal artery based forehead flap. A clinical data of 14 patients with facial soft tissue defects repaired with superficial temporal artery based forehead flaps between October 2015 and November 2022 was retrospectively analyzed. There were 9 males and 5 females with a median age of 9.5 years (range, 3-38 years). The forehead flaps were used to reconstruct facial soft tissue defects following excision of facial scar (8 cases) or congenital melanocyte nevus (6 cases). The size of defects ranged from 3 cm×2 cm to 24 cm×9 cm. Before operation, the indocyanine green angiography was used to map the superficial temporal artery and vein, and to analyze the relationship of the arteries and veins. The forehead flaps with unilateral superficial temporal fascia as the pedicle was transferred to repair the small facial defect in 2 cases. The facial pedicle contained the frontal branch of the superficial temporal artery and 2 cm of the superficial temporal fascia around the vessel, and the tiny accompanying vein of the frontal branch of the superficial temporal artery was used as the outflow of the flap. The forehead flaps with the skin pedicle including bilateral or unilateral superficial temporal fascia and the overlying skin was pre-expanded and transferred to repair the large facial defect in 12 cases. The skin pedicle contained the frontal branch of superficial temporal artery and one of main branches of superficial temporal vein. Among the 12 cases, the frontal branch of superficial temporal vein was used as the outflow in 4 cases, and the parietal branch was used as the outflow in 8 cases. The size of the flaps ranged from 3 cm×2 cm to 30 cm×13 cm. The skin pedicles were divided at 3 weeks after the flap transfer. Indocyanine green angiography could clearly showed the course and branching of the superficial temporal artery and vein. Individual differences existed in the location where the frontal branch of the superficial temporal artery entered the forehead. The superficial temporal vein had great variability and did not follow the artery. One patient had expander-related complication, which resulted in 3-cm flap necrosis. The necrotic tissue was debrided and repaired with skin grafting. The other flaps totally survived and the incisions healed by first intention. All patients were followed up 2-24 months, with a median of 11.5 months. The color, texture, and thickness of the flaps matched well with those of recipient sites. Hypertrophic scar was not observed in recipient or donor site. All patients were satisfied with the reconstructive outcomes. Indocyanine green angiography can clearly visualize the course and the branches of the superficial temporal arteries and veins, which can help surgeons understand the position, distribution, and concomitant relationship of the superficial temporal vessels, and make a rational surgical plan of the forehead flap.

Spitz tumor with RAF1 fusion: A report of 3 cases

Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation.RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

Intraoral Nevi of Gingiva - A Case Report

Intraoral nevus is a benign skin and mucosal tumour characterised by the presence of melanin-producing, neuroectodermal derived cells that can range in colour from light to dark brown, reddish brown, blue, or red. It comes in a variety of shapes, from oval to spherical. Oral melanotic nevi, which causes localised pigmentation, are a rare oral lesion. In a major survey, they were found in only 0.1 % of the population. Nevi can be acquired over time or be present from birth. Congenital nevi are hamartomas, but acquired nevi are benign neoplasms. They are most typically found on the palate, but they can also be found on the buccal mucosa, gingiva, and lips. A case report of an intramucosal nevus of gingiva in a 25-year-old woman and its surgical excision is presented in this article.

Two Cases of Giant Congenital Melanocytic Nevus - A Rare Case Report with Review of Literature

Congenital melanocytic nevus refers to a pigmented skin lesion present at birth. It is characterized by the benign growth of melanocytes in the epidermis, dermis, and subcutaneous tissue. When the lesion covers a larger area of the body, exceeding 20 cm, it is referred to as a giant congenital melanocytic nevus (GCMN). The occurrence of this condition is rare, affecting approximately 1 in every 200,000 to 500,000 births. There is a lifetime risk of 5%–40% for the development of malignant melanoma from the nevus. Early detection of the lesion and regular monitoring are crucial in order to identify any malignant changes. In this report, we present two cases of giant congenital melanocytic nevus, highlighting its rarity, and provide a literature review on the subject.

Acquired port-wine stain in an adult female: A rare entity

ABSTRACT The port-wine stain in adults, or acquired port-wine stain, is a rare entity. A fifty-year-old female presented with complaints of an asymptomatic erythematous patch affecting the right side of the face for the previous twenty years. The lesion gradually increased in size to involve the area below the eye, right nasolabial fold, cheek adjacent to the nasolabial fold, and area between the right nasolabial fold and the upper lip. On the basis of clinical and dermoscopic examinations, the diagnosis of a port-wine stain was established. Key words: Acquired port-wine stain, Female sex, Congenital nevi, Dermoscopy

Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Surgical Therapy of Congenital Nevi in the First Year of Life-Psychological Impact on Parents.

The birth of a child with a congenital melanocytic nevus (CMN) can lead to distress in the parents. Surgical treatment of CMN can begin in infancy. To provide insight into the perspective of parents of children with CMN regarding their experienced psychological burden and motivation to undergo surgery as well as their satisfaction. Retrospective analysis of patient data of infants (< 1 year of age), who were surgically treated by power stretching for CMN using subcutaneous infiltration anesthesia (SIA) from 01/01/2020 to 08/31/2021. To evaluate the parent's motivation and psychological burden during the surgical treatment of their child, a questionnaire was designed to interview them in a standardized telephone-based interview. Out of 45 interviewed parents, 62.2% indicated "severe" or "very severe" distress at the time of their child's birth. Distress was mostly reduced by information about diagnosis and treatment (n = 34) and treatment-progress (n = 27). Stigmatization was experienced by 35.6% of parents. 84,5% of parents were highly satisfied with early initiation of surgical therapy. 69% felt "very satisfied" or "satisfied" with the outcome of surgery. Motivation for surgical therapy was concern about malignant transformation of the, possible stigmatization of the child due to the nevus, while most of the parents (73.3%) mentioned both. Surgical treatment of CMN by power stretching in SIA in infancy is associated with high levels of satisfaction among the children's parents. Early initiation of surgical therapy and education about the diagnosis can reduce the psychological burden of the parents and can prevent psychosocial problems in affected children.